The carboxyl-terminal zinc-binding domain of the human papillomavirus E7 protein can be functionally replaced by the homologous sequences of the E6 protein.
The carboxyl-terminus is necessary for the functional and structural integrity of the human papillomavirus (HPV) E7 oncoprotein. Since many mutations in this domain of E7 result in the formation of unstable proteins, we have evaluated the importance of this region by replacing it with structurally related domains derived from HPV E6 proteins. Biological analysis of these mutant chimeric E7/E6 proteins showed that they retained E7-specific biological activities including cooperation with the ras oncogene to transform primary baby rat kidney cells and transcriptional activation of an E2F responsive reporter plasmid. One of the chimeric proteins was impaired in its ability to physically disrupt pRB/E2F complexes in vitro suggesting that there are defined molecular determinants in the carboxyl-terminus of E7 for this activity. In contrast, none of these proteins exhibited E6-like properties including binding to p53 and/or degradation of associated proteins.
Mavromatis
K O
KO
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, MD 20892, USA.
Jones
D L
DL
Mukherjee
R
R
Yee
C
C
Grace
M
M
Münger
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D007668:Kidney / Q000166:cytology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins; D017434:Protein Structure, Tertiary; D051381:Rats; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000378:metabolism*
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D015032:Zinc